Dosimetry Guided PRRT With 90Y-DOTATOC

NCT03013387 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2016118181R01CA167632-01
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 2 peptide receptor radionuclide therapy trial of 90Y-DOTATOC in patients with somatostatin receptor positive tumors.

Conditions

Neuroendrocrine Tumors; Meningioma; Neuroblastoma; Medulloblastoma

Outcome Measures

Primary Outcomes (2)

• Treatment efficacy as assessed by change and defined as complete response, partial response or stable disease (CR+PR+SD)

  Tumor response defined according to RECIST1.1 criteria applied on up to five target lesions (primary tumor, up to two: liver lesions, nodal metastases, and a metastatic lesion in other organs) that will be quantified and compared between pre-therapy and 3-9 months post-therapy high-resolution, contrast-enhanced CTs. 90Y-DOTATOC will be deemed worthy of further study if its associated response rate is ≥ 0.60, and clinically uninteresting if its rate is ≤ 0.40. Enrollment will proceed according to an optimal Simon two-stage study design. Sixteen (16) enrolled in the first stage; if 7 or fewer patients respond, the arm will be closed and the treatment ruled clinically uninteresting. Otherwise, an additional 30 will be enrolled. If 24 or more responses are observed in the total of 46 subjects, then the treatment will be ruled worthy. The study design has a probability of early termination equal to 0.72. Power to detect efficacy is 0.80 with a type 1 error rate of 0.05.

  Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3

• Renal, hematologic, and clinical toxicities

  Adverse events will be recorded and reported in tabular form by type and grade. If four or more subjects experience renal toxicity ≥ Grade 4, the radiopharmaceutical will be declared too toxic and the trial will be stopped. If any other irreversible Grade 4 toxicity is observed in four or more subjects, the treatment will be declared too toxic and will be stopped. Adverse events will be graded according to the most recent CTE guidelines.

  Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3

Secondary Outcomes (2)

• Determine response to therapy of lesions identified by 68Ga-DOTATOC PET/CT but not identified on Octreoscan as a confirmatory measure of true positivity of the Ga-68 DOTATOC avid lesion

  Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3

• Determine if Standard Uptake Value (SUV) on initial 68Ga-DOTATOC PET imaging correlates with SSTR2 expression as measured by quantitative messenger RNA (qPCR) or immunohistochemistry (IHC) on the diagnostic biopsy specimen

  Lesions will be quantified and compared between pre-therapy and through follow-up visits: 1) occurring 3-4 months after treatment 3 and 2) occurring 6-9 months after treatment 3

Study Arms (1)

PRRT with 90Y--DOTA-tyr3-Octreotide

EXPERIMENTAL

The 90Y--DOTA-tyr3-Octreotide initial, Cycle 1 dose will be 50 mCi/m2 in children; 120 mCi in adults. Treatment consists of 3 cycles, 6-8 weeks apart. Cycle 1 dose is fixed. Cycles 2 and 3 doses will be determined by dosimetry-based calculation of renal doses from previous cycles; total renal dose ≤ 23Gy. 90Y-DOTA-tyr3-Octreotide will be administered with an amino acid solution to prevent radiation damage to kidneys. Amino acid infusion will begin 30 min prior to infusion of 90Y-DOTATOC and continue 3.5 hrs after infusion of study drugs. 68Ga-DOTATOC will be administered intravenously to perform the PET/CT scan. The dose will be 3-5 mCi (target 4mCi). The pediatric dose will be 0.043 mCi/kg with a minimum dose of 0.3 mCi and a maximum dose of 3 mCi in children \<18 years old.

Radiation: 90Y-DOTA-3-tyr-Octreotide; Procedure: Positron Emission Tomography (PET) whole body scan; Drug: Amino Acids

Interventions

90Y-DOTA-3-tyr-Octreotide RADIATION

90Y-DOTATOC is a radiopharmaceutical that will be used l as a treatment for both children and adults with neuroendocrine and other somatostatin receptor positive tumors.

Also known as: 90Y-DOTATOC

PRRT with 90Y--DOTA-tyr3-Octreotide

Positron Emission Tomography (PET) whole body scan PROCEDURE

68Ga-DOTATOC is a radiopharmaceutical used in PET scans to identify tumors as it can adhere to Somatostatin Receptors.

Also known as: 68Ga-DOTATOC PET

PRRT with 90Y--DOTA-tyr3-Octreotide

Amino Acids DRUG

This is a solution of amino acids that will decrease the amount of 90Y-DOTATOC that recirculates through the body after injection, therefore decreasing radiation dose to the kidneys.

Also known as: Lysine and Arginine

PRRT with 90Y--DOTA-tyr3-Octreotide

Eligibility Criteria

• Age: 6 Months - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or Sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy.
• Participation in Iowa Neuroendocrine Tumor Registry.
• A pathologically confirmed (histology or cytology) malignant neoplasm with at least one target lesion that is confirmed by conventional imaging (CT or MRI) and is determined to express somatostatin receptors by 68Ga-DOTATOC (TATE) PET within 120 days prior to entry into the trial.
• The target lesion is one that either has never received external beam radiation or has been previously irradiated and has since demonstrated progression. Any local irradiation of the target lesion or any non-target lesions via external beam, conformal or stereotactic radiation treatments must have occurred more than 4 weeks prior to study drug administration. Any full cranial-spinal radiation, whether or not a target lesion is included in the field, must have occurred more than 3 months prior to study drug administration.
• Life expectancy \> 2 months at the time of study drug administration.
• Archival tissue from a previous biopsy will be required.
• Age ≥ 6 months-90 years at the time of study drug administration.
• Performance status as determined by Karnofsky ≥ 60 or Lansky Play Scale ≥ 60% at the time of study drug administration.
• Completion of Norfolk Quality of Life Questionnaire.
• Within 7-10 days of study drug administration, patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1000/mm3
• Platelets ≥90,000/mm3
• total bilirubin \<3X ULN for age
• AST(SGOT) \& ALT(SGPT) ≤10X institutional upper limit of normal for age
• Urinalysis no greater than 1+ hematuria or proteinuria. Adults(age18 or \>): Serum creatinine ≤ 1.2 mg/dl; if serum creatinine is \>1.2 mg/dL,nuclear GFR will be measured. GFR will need to be ≥ 80 ml/min/1.73m2 for subjects ≤40 years old,

You may not qualify if:

• Pregnant women are excluded from this study because 90Y-DOTATOC is a Class C agent with potential teratogenic or abortifacient effects.
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 90Y-DOTATOC, breastfeeding should be discontinued until 6 weeks after the last administration of study drug.
• Surgery within 4 weeks of study drug administration.
• External beam radiation to both kidneys (scatter doses of \<500 cGy to a single kidney or radiation to \< 50% of a single kidney is acceptable).
• Prior PRRT with 90Y-DOTATOC (TATE) or 177Lu-DOTATOC (TATE) or 131I-MIBG therapy for this malignancy.
• Another investigational drug within 4 weeks of study drug administration.
• Concurrent, malignant disease for which patient is on active therapy.
• Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol.
• Any subject for whom, in the opinion of their physician, a 12-hour discontinuation of somatostatin analogue therapy represents a health risk. Also subjects who have received long-acting somatostatin analogue in the past 28 days or long-acting lanreotide within the past 8 weeks are excluded. Subjects may be maintained on short acting octreotide during the time from last injection of long-acting somatostatin analogue until 12 hrs prior to injection of study drug. Known antibodies to Octreotide, Lanreotide, or DOTATOC or history of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-DOTATOC.
• Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of study drug administration or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subject weighs more than 450 pounds. (Subjects who weigh more than 450 pounds will not be able to fit inside the imaging machines.)
• Inability to lie still for the entire imaging time (due to cough, severe arthritis, etc.)

Sponsors & Collaborators

• Sue O'Dorisio: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Meningioma; Neuroblastoma; Medulloblastoma

Interventions

90Y-octreotide, DOTA-Tyr(3)-; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Whole Body Imaging; Amino Acids; arginyllysine

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Glioma

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Amino Acids, Peptides, and Proteins

Study Officials

• M S O'Dorisio, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: January 6, 2017
• Study Start: January 1, 2017
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2019
• Last Updated: August 25, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share